Antitumor Activity of cGAMP via Stimulation of cGAS-cGAMP-STING-IRF3 Mediated Innate Immune Response | Academic Article individual record
abstract

Immunotherapy is one of the key strategies for cancer treatment. The cGAS-cGAMP-STING-IRF3 pathway of cytosolic DNA sensing plays a pivotal role in antiviral defense. We report that the STING activator cGAMP possesses significant antitumor activity in mice by triggering the STING-dependent pathway directly. cGAMP enhances innate immune responses by inducing production of cytokines such as interferon-β, interferon-γ, and stimulating dendritic cells activation, which induces the cross-priming of CD8(+) T cells. The antitumor mechanism of cGAMP was verified by STING and IRF3, which were up-regulated upon cGAMP treatment. STING-deficiency dramatically reduced the antitumor effect of cGAMP. Furthermore, cGAMP improved the antitumor activity of 5-FU, and clearly reduced the toxicity of 5-FU. These results demonstrated that cGAMP is a novel antitumor agent and has potential applications in cancer immunotherapy.

authors
author list (cited authors)
Li, T., Cheng, H., Yuan, H., Xu, Q., Shu, C., Zhang, Y., ... Tan, X.
publication date
2016
published in
keywords
  • Apoptosis
  • Interferon Regulatory Factor-3
  • Mice, Inbred BALB C
  • Antineoplastic Agents
  • Animals
  • Nucleotides, Cyclic
  • Cytokines
  • Cell Line, Tumor
  • Immunity, Innate
  • Dendritic Cells
  • Fluorouracil
  • Membrane Proteins
  • Nucleotidyltransferases
altmetric score

6.0

citation count

80